The most common complication of antibiotic therapy is Complications after antibiotic treatment

The use of antibiotics (AB), like other drugs, is associated with the risk of side effects. Side effects of AB can be varied: overdose, specific side effects, intolerance, secondary drug effect, drug interactions, idiosyncrasy, psychogenic reactions, teratogenic and carcinogenic effects, allergic and pseudo-allergic reactions.

Most of them are due to doctor's mistakes: inattention to the indicated direct toxic side effects, ignoring concomitant pathology, incorrect combination of drugs, etc.

Allergies. They occur when using all groups of drugs, but are most characteristic of β-lactams. Cross-allergic reactions with some antibiotics (for example, β-lactams) are pronounced, but their theoretical likelihood is not an absolute contraindication to the use of the subsequent group of the β-lactam drug.

Complications of chemotherapeutic action

• bacteriolysis reaction- in fact, an infectious-toxic shock in response to the release of endotoxin during the massive destruction of microbes after giving a loading dose of bactericidal AB. Most significant when using antibiotics that cause rapid lysis and filamentation of bacteria (penicillins, cephalosporins, quinolones); practically absent in carbapenems (spheroplast transformation of bacteria), monobactams, aminoglycosides and polymyxins (prototype of endotoxin-binding ABs).
• Dysbiosis- inhibition of normal biocenosis with the development of superinfections, more often UPM flora: staphylococcal enterocolitis, candidiasis, pseudomembranous colitis (PMC) caused by Cl. difficile, etc.
• Suppression by some AB of various links immunity naturally developed by the body in response to infection.

Direct specific effect on the body

Toxicity, as a rule, is dose-dependent, manifests itself with long courses and disappears after drug withdrawal. However, there are irreversible (eg, aminoglycoside-induced ototoxicity) and non-dependent (aplastic anemia with chloramphenicol use) effects.

Due to the serious effect on the growing organism, a number of ABs are not recommended for use. in children- tetracyclines (impair the growth of bones and teeth), chloramphenicol (myelotoxic effect, "gray collapse" in newborns), fluoroquinolones (alleged violation of the growth of bones and cartilage), sulfonamides (myelotoxic effect, displacement of bilirubin from albumin).

Many drugs in high concentration, which is created on the surface of the brain or spinal cord, have a toxic effect on the central nervous system. For example, penicillins can cause epileptic seizures and encephalopathy. There are reports that paresthesia, sciatica and transverse myelitis have occurred with the endolumbar administration of a number of drugs. There are also cases of arachnoiditis after repeated intrathecal administration of antibiotics.

Characterization of complications of antibiotic therapy based on different groups of antibacterial drugs

The characteristics of the complications of antibiotic therapy based on different groups of antibacterial drugs are presented in Table. 2.

Possible side effects of antibiotics

side effect	which group is most typical
allergic reactions (most often skin reactions: itching, dermatitis, in rare cases - up to anaphylactic shock)		b-lactams
eosinophilia and changes in the biochemical blood test (usually a slight and transient increase in transaminases, creatinine, urea, etc.)		for all AB groups
abdominal pain, nausea, loss of appetite, nonspecific diarrhea, other dyspeptic disorders	when administered orally: macrolides (especially erythromycin), tetracyclines, fluoroquinolones, lincosamides (especially clindamycin), nitrofurans, rifampicin, nitroimidazoles
nephrotoxic effect (usually - changes in the general analysis of urine)	aminoglycosides, some cephalosporins (cephalothin, cefamandol), polymyxins (for parenteral use)
ototoxicity	aminoglycosides
candidiasis and dysbacteriosis	for all AB groups with long-term use
oppression of hematopoiesis
suppression of the immune system	chloramphenicol, co-trimoxazole, sulfonamides
growth inhibition connective tissue (cartilage, ligaments, teeth)	fluoroquinolones, tetracyclines
inhibition of the blood coagulation system	"antipseudomonas" penicillins, parenteral cephalosporins with MTT group (cefoperazone, cefamandol, cefotetan, cefmetazole)
neurotoxicity	nitrofurans, polymyxin B, nitroimidazoles, fluoroquinolones, lincosamides, sisomycin
pseudomembranous colitis	clindamycin, aminopenicillins, cephalosporins II-III (especially oral)

Some side effects of different groups of antibiotics

penicillins	low toxicity, but: high risk of allergic reactions possible development of intestinal dysbiosis in high doses possible. convulsions and other manifestations of encephalopathy
cephalosporins	low toxicity: allergic reactions (sometimes cross with penicillins) and intestinal dysbiosis (before MVP) transient thrombo-, neutropenia and interstitial nephritis with long-term courses (not recommended to be combined with nephrotoxic drugs, primarily loop diuretics) hypoprothrombinemia (cefamandol, cefoperazone) disulfiram-like action when taking alcohol (cefoperazone)
carbapenems	low toxicity: intestinal dyspepsia imipenem increases the convulsive readiness of the central nervous system partially cross-allergic with other β-lactams
amino glycosides	toxic(toxicity decreases from I to III generation): nephrotoxicity - damage to proxima. tubules - develops in 5-30%, is always reversible (the risk is high in the elderly, with nephropathology, long-term therapy and in combination with nephrotoxic drugs - loop diuretics, glycopeptides, etc.) otovestibulotoxicity (ototoxicity is irreversible, caution is required when prescribing to persons with existing otopathology) use together with muscle relaxants may lead to the development of neuromuscular blockade with respiratory failure potential teratogenicity
macrolides	low toxicity: mild dyspepsia phlebitis with intravenous administration of erythromycin
fluoroquinolones	low toxicity: not recommended for use without strict indications in children under 12 years of age due to a theoretically possible toxic effect on the growing connective tissue (arthrotoxicity has been shown in experiments on immature animals) photosensitivity with the development of dermatosis is possible mild dyspepsia headaches, QT prolongation, cardiac arrhythmias
lincosamides	significant side effects: there is a high probability of developing intestinal dysbiosis, up to MVP (including with parenteral administration, and after local applications), more often when using lincomycin - therefore, they are used only as reserve drugs
tetracyclines	toxic: in high doses cause pancreatitis and hepatic steatosis potential teratogenicity
chloramphenicol	toxic: aplastic anemia (occurs 1:40.000, dose-independent, may develop after discontinuation of the drug, absolutely fatal) hematopoietic toxicity (primary effect on the red germ, significant at courses> 10 days, reversible) gray syndrome (grey child) - acute circulatory collapse in case of overdose (often in newborns up to 1 month of life due to low activity of the glucuronidase that metabolizes it) intestinal dyspepsia when taken orally
glycopeptides	highly toxic: nephrotoxicity (hematuria, proteinuria, or even acute renal failure when combined with aminoglycosides or when used >3 weeks at a high dose) hematological disorders (transient neutro-, thrombopenia) ototoxicity various allergic reactions, up to shock local infusion-related manifestations (thrombophlebitis, red-man syndrome (red neck): with rapid intravenous administration of the drug - redness of the skin of the shoulder girdle, spasm of the pectoral muscles and difficulty breathing) cardiovascular (hypotension, cardiac arrest described)
sulfonamides	toxic: skin reactions (to toxic epidermolysis syndrome) kernicterus when used in children under 2 months of age, especially in premature infants or those with physiological jaundice (theoretically, sulfanilamide prevents the binding of bilirubin to serum albumin) depression of hematopoiesis (neutro- and thrombopenia) nephrotoxicity hepatotoxicity, dyspepsia
co-trimoxazole	side effects are mainly due to the sulfanilamide component
nitro imidazoles	metallic taste in the mouth and indigestion dizziness, paresthesia (with prolonged use in high doses, peripheral neuropathy may develop) risk of developing neutropenia phlebitis with / in the introduction

Complications of antibiotic therapy
allergic reactions
Toxic effect of antibiotics
Adverse reactions due to the direct pharmacodynamic action of antibiotics

ALLERGIC REACTIONS

Allergy is understood as an altered reaction of the body to the action of foreign substances that occurs after previous contact with them or as a result of a high hereditary sensitivity of the body (Cooke, 1935).
Allergic reactions are not related to the pharmacological properties of drugs and occur only in people with hypersensitivity (often sensitized).

In the body's immune response to any antigen, a sensitization phase (preparatory) and a manifestation phase are distinguished. Allergy develops progressively: 1) the emergence of antibodies in response to antigenic stimulation;
2) the formation of an antigen-antibody complex in tissues, causing a rapid release of biologically active substances - histamine, heparin, serotonin; 3) the effect of these substances on blood vessels, bronchi, and the nervous system.
Stages II and III are non-specific and the same when exposed to any stimulus (antigen). This explains the stereotype of allergic reactions, the intensity and duration of which depend on the localization of the reaction and the body's immune capabilities.

The antigenic properties of antibiotics are explained by the fact that they are the so-called. incomplete antigens - haptens (simple chemical compounds). Haptens acquire antigenic properties only after binding to a protein in the body.
It does this by binding to soluble proteins in the blood or cell membranes. It has been established that antibodies to penicillin belong to the classes IgG, IgM, IgE.

Clinical manifestations of allergic reactions can be realized immediately (these are the most dangerous reactions) or be of a delayed type.
The main trigger of allergic reactions is tissue damage by an immunological antigen-antibody reaction. At the same time, proteolytic and lipolytic enzymes are activated, histamine, serotonin and other biologically active substances are released. They have a special effect on the apparatus of the nervous system, cause increased vascular permeability, spasm of the smooth muscles of the bronchi, increase the hydrophilicity of the fibers of the loose connective tissue, contributing to the occurrence of extensive edema. These pathogenetic mechanisms give allergic reactions a special, sometimes very bright color and determine a complex set of clinical manifestations.

We have already emphasized that allergic reactions reflect the individual properties of the organism, and not the pharmacological characteristics of the drug. However, more often these reactions occur with repeated administration of certain substances that sensitize the body, even with the introduction of negligible amounts.
(hundredths and thousandths of a gram). The state of sensitization can persist for many months and years. Sensitization can also be caused by chemicals that are similar in structure (“cross-sensitization”). An example is cross-sensitization with sulfonamides, streptomycin and penicillin. This phenomenon explains the occurrence of severe allergic reactions and even anaphylactic shock at the first
(single) administration of penicillin. It has now been established that in the development of allergic reactions to drugs, an individual predisposition, usually a family one, is important - the allergic constitution.

Types of allergic reactions.

Anaphylactic shock

Anaphylactic shock is the most formidable complication requiring rapid diagnosis and immediate treatment. It usually develops very quickly. It may be preceded by prodromal phenomena: itching, urticaria, angioedema.

The main symptoms of anaphylactic shock are: a drop in blood pressure up to collapse with tachycardia or bradycardia, loss of consciousness, swelling of the face and mucous membranes, urticaria, rarely vomiting and diarrhea.
In severe forms, intestinal bleeding, dyspnea, cerebral edema, liver damage, and coma are observed. The predisposition of the organism to the development of shock is more pronounced in patients who previously suffered from various allergic diseases (bronchial asthma, hay fever, etc.).

Death from anaphylactic shock can occur in the first minutes and hours after the administration of an antibiotic. However, cases are described when patients died a few days or weeks after the end of treatment.

Serum sickness syndrome.

Severe, sometimes irreversible or difficult to eliminate reactions of a generalized nature include the so-called serum sickness, manifested by various skin reactions, angioedema, joint pain, arthralgia, fever, blood eosinophilia, enlargement of the spleen and lymph nodes. The earliest symptom is swelling of the lymph nodes, sometimes in combination with an inflammatory-necrotic reaction at the injection site. (phenomenon of Artyus-Sakharov). In most cases, when antibiotic therapy is stopped, the serum sickness syndrome disappears without special treatment. In protracted cases, desensitizing therapy, the use of antihistamines and hormonal drugs are indicated.

Skin lesions.
Skin and mucous membrane lesions of an allergic nature can be of a different nature.
Rash - macular, spotty roseola, maculopapular, maculopapular, spotty (like scarlet fever) - more often appears with the introduction of penicillin to patients with hypersensitivity or previously sensitized. These reactions are easily eliminated and disappear after the abolition of the antibiotic and the appointment of deallergizing agents (diphenhydramine, pipolfen, calcium chloride). However, in rare cases, reactions from the skin and mucous membranes are very persistent, and long-term treatment is required with the use of active and potent deallergizing agents. The most effective use of corticosteroid hormones - prednisone, prednisolone, triamcinolone, etc. - in doses dictated by the severity of the allergic reaction.

Dermatitis: erythematous, urticarial or bullous rash (exfoliative dermatitis, sometimes generalized) Contact dermatitis is most often found in antibiotic workers and medical personnel who have constant contact with an antibiotic (especially penicillin, streptomycin, tetracycline, chloramphenicol, as well as other antibiotics). Contact dermatitis can also occur when ointments or solutions containing antibiotics are applied to the skin, administered intradermally or subcutaneously to determine sensitization to drugs.

Urticaria can be observed both after local and after systemic
(parenteral, orally) administration of antibiotics and is one of the most frequent allergic complications of antibiotic therapy (most often with penicillin therapy). Urticaria occurs early (minutes, hours), and sometimes many days or weeks after antibiotic administration.

Angioedema (Quincke's edema) is localized (swelling of the lips, eyelids, face) or extends to a number of areas (larynx, trachea, lungs). Angioedema may be of independent significance or be an integral part of a general allergic reaction to the administration of antibiotics.

Photodermatosis is a skin lesion caused by certain antibacterial drugs that occurs after exposure to sunlight.

The skin test is as follows. A drop of an antibiotic solution containing 100-1000 IU of the drug is applied to the flexor surface of the forearm and the skin is scarified, as is done with the Pirquet test. If through
15 minutes later, redness appears more than 1 cm in diameter, the reaction is assessed as weakly positive (+), if the redness and papule are positive (++), if multiple papules, vesicles, diffuse hyperemia are sharply positive (+++). In cases of sharply increased sensitivity, a general reaction may occur - urticaria, urticaria rash all over the body, etc.
An intradermal test consists in the intradermal administration of an antibiotic solution (200-2000 units of penicillin) in 0.2 ml of saline.
An antibiotic is injected on the flexor surface of the forearm, on the other hand in a symmetrical area, 0.2 ml of saline is injected. The appearance of hyperemia (the size of a papule is more than 3 kopecks), swelling, and sometimes rashes at the injection site is regarded as a positive test.
Skin tests do not always give an immediate reaction: it can manifest itself through
24-48 hours.

TOXIC EFFECT OF ANTIBIOTICS.
Neurotoxic reactions
Neurotoxic phenomena occur after the use of antibiotics of a number of groups and manifest themselves:

1) damage to the auditory branches of the VIII pair of cranial nerves (monomycin, kanamycin, neomycin, streptomycin, florimycin, ristomycin);

2) action on the vestibular apparatus (streptomycin, florimycin, kanamycin, neomycin, gentamicin). The toxic effect of streptomycin and other aminoglycosides on the VIII pair of cranial nerves is expressed in hearing loss and vestibular disorders. In the nature of lesions of the organ of hearing, there is a difference between streptomycin and neomycin. In the treatment of streptomycin, these reactions are mostly temporary (in some cases, persistent and progressive damage to the VIII pair of cranial nerves may be detected). Many TB patients are able to tolerate streptomycin injections without complications for several months.
Neomycin causes complications much more often, to a more pronounced and stable degree. They can occur after 7-10 days of using this drug. Given this fact, neomycin can only be applied topically and inside;

3) damage to the optic nerve (streptomycin, levomycetin, cycloserine, polymyxin);

4) the development of polyneuritis (streptomycin, polymyxin, amphotericin B, cycloserine);

5) the occurrence of paresthesia, headaches, dizziness, ataxia
(polymyxin, streptomycin, cycloserine, amphotericin B);

6) the development of various lesions of the central nervous system
(cycloserine, polymyxin, griseofulvin, amphotericin B, penicillin, streptomycin);

7) the occurrence of neuromuscular blockade (aminoglycosides, polymyxin);

8) direct toxic effect with intralumbar administration, manifested in the form of hallucinations, epileptiform seizures, convulsions of individual muscle groups and general muscle hypertension (penicillin, streptomycin, tetracycline, chloramphenicol and a number of other antibiotics).
Neurotoxic reactions can be observed when prescribing large doses of benzylpenicillin (intravenously more than 40,000,000 IU per day).

Nephrotoxic reactions may accompany treatment with polymyxin, amphotericin B, neomycin, monomycin, kanamycin, gentamicin, sisomycin, tobramycin, streptomycin, cephaloridine, griseofulvin, ristomycin, sulfonamides.

Patients with impaired renal excretory function are particularly susceptible to the nephrotoxic effect of drugs, which is associated with their cumulation and the creation of high concentrations in the blood due to impaired excretion. In violation of the excretory function of the kidneys, the nephrotoxicity of many drugs increases with the simultaneous spread of the toxic effect on the liver. In these cases, it is necessary to prescribe drugs with a less pronounced nephrotoxic effect, primarily penicillins and cephalosporins.
Penicillins - natural and their semi-synthetic derivatives - are relatively low-toxic even in large doses.

Cephalosporins. Nephrotoxic reactions are most often observed with the use of "old" cephalosporins: cephalothin and cephaloridine (the latter with greater frequency). When using cephaloridine in high doses, severe lesions of the renal tubules (up to necrosis) are described. The incidence and severity of nephrotoxicity increases with the combination of cephalosporins with aminoglycosides. For cephalosporins II and III generations (cefazodin, cefamandol, cefoxitin, cefuroxime, etc.), these reactions are less typical.
Aminoglycosides. Nephrotoxicity refers to one of the side effects of this group of antibiotics. Among the most commonly used parenteral aminoglycosides, kanamycin and gentamicin and other newer aminoglycosides (tobramycin, sisomycin, amikacin) are effective drugs.
With long-term treatment with these drugs and in doses exceeding the usual daily dose, lesions of the proximal tubules can be observed, which is clinically expressed in a decrease in glomerular filtration, the appearance of albuminuria, microhematuria, enzymuria. The use of these antibiotics in renal failure requires great caution. When prescribing aminoglycosides, it is necessary to constantly monitor kidney function and choose the optimal daily dose of antibiotics according to the criterion of both effectiveness and safety.
Polymyxins are nephrotoxic, but with normal renal function and careful dose selection, these effects can be minimized.
Ristomycin, viomycin (florimycin) are potentially nephrotoxic substances. These drugs should only be used when other less toxic antibiotics have not been effective.
Tetracyclines do not have a direct nephrotoxic effect, however, in patients with renal insufficiency, the level of urea in the blood may increase. In severe renal failure, tetracyclines can cause azotemia, acidosis, and vomiting. When using expired tetracycline preparations, which contain degradation products - anhydrotetracycline and epianhydrotetracycline, Fanconi syndrome (nausea, vomiting, albuminuria, acidosis, glucosuria, aminoaciduria) may develop. At the same time, degenerative changes are observed in the distal parts of the renal tubules; glomeruli remain intact. The phenomena are usually reversible.

Hepatotoxic events. Many antibiotics accumulate in high concentrations in bile (tetracyclines, erythromycin, rifampicin) and can cause liver damage.
Hepatitis associated with direct toxic or toxic-allergic action of sulfonamides has been described. Since the liver has a detoxifying function, and the kidneys have an excretory function, often both of these organs can be a simultaneous object of side effects of drugs. With any dysfunction of these systems, the possibility of developing toxic side effects should be borne in mind.
In accordance with this, the physician should carefully monitor the development of these symptoms and choose a less toxic agent, reduce the dose, or avoid prescribing drugs with possible side effects on the liver and kidneys. With the use of amphotericin B, hepatitis may occur, with the appointment of nitrofurans, lincomycin - the phenomenon of jaundice; in the treatment of some salts of erythromycin (estolate) - cholestatic hepatitis.

Severe liver damage in the form of fatty infiltration of the liver cells can be observed with the use of large doses of tetracyclines, especially those administered parenterally. Although these phenomena are usually reversible, if the patient has a history of organic liver damage or if hepatotoxic events are detected during the use of tetracyclines, the antibiotic should be canceled. To prevent the possibility of liver damage, it is not recommended to administer intravenous tetracycline in a daily dose of more than 1 g.

Described lesions of the liver and pancreas in the treatment of tetracyclines in women suffering from pyelonephritis during pregnancy.

The hepatocellular form of drug jaundice is characteristic of griseofulvin, streptomycin, tetracyclines, amphotericin B, florimycin and other drugs. Side effects stop after discontinuation of the drug.
Toxic effect on the gastrointestinal tract of a number of antibiotics
(tetracycline, erythromycin, griseofulvin, amphotericin B, fuzidine, etc.), associated with their irritating effect on the mucous membranes, manifests itself in the form of nausea, vomiting, anorexia, pain in the abdomen, diarrhea, etc.
Usually these phenomena are not so pronounced as to cancel antibiotics. However, with often joining dysbacteriosis under the influence of broad-spectrum antibiotics, as well as lincomycin and clindamycin, serious complications can occur, up to pseudomembranous enterocolitis.
Influence on the hematopoietic system. Inhibition of hematopoiesis in the form of hypoplastic anemia is observed in rare cases with the use of levomycetin and amphotericin B, hemolytic anemia with the use of levomycetin, streptomycin, aplastic anemia with the use of levomycetin. Leukopenia with agranulocytosis is described in the treatment of chloramphenicol, ristomycin, griseofulvin, thrombocytopenia - with the use of ristomycin, chloramphenicol, rifampicin. As a rule, hematopoiesis is restored after the cessation of treatment. Severe bone marrow lesions are observed during treatment with chloramphenicol, especially with its long-term use.

In the development of agranulocytosis and hypoplasia of hematopoiesis, the role of autoimmune mechanisms or a decrease in the resistance of blood cells to drugs due to enzyme deficiency cannot be excluded (by the type of development of some hemolytic anemias, for example, drug-induced hemoglobinuria, etc.). Given the great rarity of hematopoietic hypoplasia during antibiotic treatment, some authors raise the question that this complication occurs in individuals who already have a genetic defect in bone marrow hematopoiesis. Antibiotics in this case can play the role of a push in the implementation of the process.

With the greatest frequency, severe lesions of hematopoiesis (aplastic anemia) occur under the influence of chloramphenicol. Anemia may be hypoplastic or aplastic with thrombocytopenia and agranulocytosis leading to death. Based on the possibility of such severe phenomena, indications for the use of chloramphenicol should be strictly limited and the drug should be used only under the supervision of a doctor, in a hospital, in cases where other, less toxic substances cannot be prescribed.

The embryotoxic effect of antibiotics is a side effect of drugs on the fetus associated with their penetration through the placental barrier. Described cases of hearing loss in newborns in the treatment of pregnant women with streptomycin, hearing and kidney damage in the treatment of neomycin and kanamycin. Under the influence of tetracycline, when administered to pregnant women, pigmentation of the teeth and damage to tooth enamel can occur, an increased tendency to caries in children. The effect on the growth of fetal bones (deceleration of skeletal formation) is described when large doses of tetracyclines are administered to pregnant women. Due to the possibility of toxic effects on the fetus for 3-6 weeks. before childbirth, the use of chloramphenicol, tetracycline, streptomycin, kanamycin and other drugs is contraindicated.

This group includes superinfections and nosocomial infections caused by the biological action of antibiotics, as well as side effects associated with a violation of the composition of the so-called normal microflora of the patient's body (dysbacteriosis), bacteriolysis reaction
(Yarish-Herksheimer).

Superinfections can be both endogenous and exogenous. In the process of antibiotic therapy, which provides a cure for the main process, the normal microflora that is sensitive to the prescribed drugs is simultaneously suppressed. Many apathogenic or opportunistic microorganisms begin to multiply intensively, and can become a source of a new disease.
(endogenous superinfection).

Endogenous superinfections can be caused by various microorganisms - staphylococci, Pseudomonas aeruginosa, Proteus, Enterobacter, serrations, Escherichia coli, anaerobes, pathogenic fungi, etc., which are naturally insensitive to this antibiotic or have acquired resistance during antibiotic therapy.

The form of the course of superinfections and their localization can be different: meningitis, brain abscesses (due to endocarditis and sepsis), lesions of the urinary tract, gastrointestinal tract, biliary tract, respiratory tract, ENT organs, mucous membranes and skin, eyes, etc. d.

Exogenous superinfection (as a result of secondary infection) may be due to the same type of microorganism that causes the main pathological process, but with a different degree of sensitivity to antibiotics, as well as a new type of pathogen. This phenomenon is observed in the treatment of diphtheria, pneumonia, tuberculosis, scarlet fever and can serve as a source of new complications in this patient.

Exogenous infection is transmitted by air or by direct contact. The source of infection is the nasopharynx of patients and staff, indoor air, medical instruments, etc.
Candidiasis. This group of superinfections includes diseases caused by yeast-like fungi of the genus Candida. Antibiotic therapy (especially the use of broad-spectrum drugs) violates the usual ratios between various representatives of the normal microflora
(suppression of bacterial growth and increased reproduction of yeast-like fungi) and contributes to the activation of Candida and their spread in debilitated patients.

In accordance with the classification of A. N. Arabian, the following main forms of candidiasis are distinguished.

A. Candidiasis of the external integument: skin lesions, lesions of the skin appendages
(nails and periungual rollers, scalp); lesions of the mucous membrane (oral cavity and mucous membranes of the external genital organs).

B. Visceral, systemic candidiasis: respiratory tract, gastrointestinal tract, genitourinary system, muscular system, skeletal system, cardiovascular system, nervous system; ENT organs, the organ of vision, systemic diseases of organs, septicopyemic forms with damage to many organs.

B. Common and localized levurides.

D Candidal complications.

In turn, visceral candidiasis is divided (A M Arievich) into the following groups:

1) primary candidiasis;

2) secondary candidiasis (superinfection);
3) terminal candidiasis that occurs in chronic and malnourished patients.
Candidiasis most often affects newborns who do not have sufficiently developed protective reactions, as well as sharply weakened patients with profound metabolic disorders.
It should be noted that the seeding of Candida from the mucous membranes, from sputum, feces, urine is observed and is normal, without connection with the use of antibiotics. In the terminal stages of the disease in persons sharply weakened by the underlying disease, generalized Candida invasion can occur with damage to internal organs and without the intervention of antibiotics. The probability of candidasepsis in the treatment of antibiotics in percentage terms is low. However, an exaggerated fear of possible candidiasis leads in some medical institutions to refuse antibiotic therapy, even in cases where there are mandatory or vital indications for the massive use of antibiotics.
Local candidiasis, superficial lesions of the mucous membranes are not dangerous and usually should not be a signal to stop antibiotic treatment. Meanwhile, in a number of cases, with a clear therapeutic effect from the applied antibiotic, it is unreasonably canceled when thrush appears on the oral mucosa in a patient
(white plaque) or individual candidiasis elements.
The abolition of broad-spectrum antibiotics and their replacement with others, with a narrower focus of action, in accordance with the ethnology of the disease, the introduction of nystatin or levorin in combination with vitamins completely cure patients from local candidiasis.
However, reasonable care must be taken both clinically and in the laboratory. It is necessary to eliminate in every possible way the factors contributing to the development of candidiasis, improve the nutrition and vitamin balance of patients, and activate protective mechanisms. If necessary, measures such as steroid therapy and blood transfusion should be taken, vigorously treat the underlying disease, carefully monitor the condition of the mucous membranes. The rapid spread of lesions of the mucous membranes and skin, the increasing number of Candida in cultures of scrapings from mucous membranes, urine, sputum and feces are signals of the possibility of developing severe candidal lesions. In such cases, when deciding on the further continuation of antibiotic therapy, one should approach the patient strictly individually, assessing the state of the underlying process. At the first signs of generalization of a fungal infection (detection of mycelium during microscopy of native urine preparations, sputum of exudates of cavities, etc., an increase in mycelial and cellular elements during repeated examinations; the appearance of clinical symptoms of candidal sepsis or lesions of visceral organs), the introduction of antibacterial antibiotics is immediately stopped and treated with antifungal drugs

Treating candidiasis is challenging, although it usually regresses when antibiotics are discontinued.

The bacteriolysis reaction is the Jarisch-Herxheimer reaction (“therapeutic shock”).
In the antibiotic therapy of some infections, peculiar complications are possible associated with the rapid destruction of microbes and the release of a large amount of endotoxins. These phenomena are usually observed at the beginning of antibiotic therapy with the introduction of large doses of bactericidal and bacteriostatic antibiotics.

They develop rapidly, beginning with tremendous chills, fever, tachycardia, profuse sweat; possible diarrhea. In severe cases, there is a decrease in temperature, collapse, loss of consciousness, oliguria, anuria, if left untreated, death can occur Symptoms of the bacteriolysis reaction resemble the phenomena observed in endotoxic and blood transfusion shock

The formation of endotoxins is characteristic of the following pathogens of infectious diseases: Salmonella, Shigella, Brucella, Escherichia coli, Pseudomonas aeruginosa, Proteus, Whooping Cough, Pasteurella, Spirochetes, Mycobacteria

Manifestations of bacteriolysis reactions of varying intensity are described in the antibiotic therapy of typhoid fever, whooping cough, syphilis, brucellosis, leptospirosis, etc. Usually, symptoms of intoxication appear soon after the administration of the antibiotic, and their occurrence indicates a high sensitivity of the pathogen to this etiotropic agent

In most cases, the development of severe reactions of bacteriolysis can be prevented by observing the antibiotic therapy regimen, by combining the use of antibiotics with antihistamines, etc.

№ 41 Complications of antibiotic therapy, their prevention.
Like any drug, almost every group of antimicrobial chemotherapy drugs can have side effects, both on the macroorganism and on microbes, and other drugs.
Complications from the microorganism
The most common complications of antimicrobial chemotherapy are:
Toxic effect of drugs . As a rule, the development of this complication depends on the properties of the drug itself, its dose, route of administration, the patient's condition and manifests itself only with prolonged and systematic use of antimicrobial chemotherapeutic drugs, when conditions are created for their accumulation in the body. Especially often such complications occur when the target of the drug is processes or structures that are similar in composition or structure to similar structures of macroorganism cells. Children, pregnant women, as well as patients with impaired liver and kidney function are especially susceptible to the toxic effect of antimicrobial drugs.
Adverse toxic effects can manifest as neurotoxic (for example, glycopeptides and aminoglycosides have an ototoxic effect, up to complete hearing loss due to effects on the auditory nerve); nephrotoxic (polyenes, polypeptides, aminoglycosides, macrolides, glycopeptides, sulfonamides); general toxic (antifungal drugs - polyenes, imidazoles); oppression of hematopoiesis (tetracyclines, sulfonamides, levomycetin / chloramphenicol, which contains nitrobenzene - a suppressor of bone marrow function); teratogenic [aminoglycosides, tetracyclines disrupt the development of bones, cartilage in the fetus and children, the formation of tooth enamel (brown teeth), levomycetin / chloramphenicol is toxic to newborns in which liver enzymes are not fully formed ("grey baby syndrome"), quinolones - act on developing cartilage and connective tissue].
Warningcomplications consists in the rejection of drugs that are contraindicated for this patient, control over the state of the functions of the liver, kidneys, etc.
Dysbiosis (dysbacteriosis) . Antimicrobial chemotherapy drugs, especially broad-spectrum ones, can affect not only infectious agents, but also sensitive microorganisms of the normal microflora. As a result, dysbiosis is formed, therefore, the functions of the gastrointestinal tract are disturbed, beriberi occurs, and a secondary infection may develop (including endogenous, for example, candidiasis, pseudomembranous colitis). ). Prevention of the consequences of such complications consists in prescribing, if possible, drugs with a narrow spectrum of action, combining the treatment of the underlying disease with antifungal therapy (for example, the appointment of nystatin), vitamin therapy, the use of eubiotics, etc.
Negative effect on the immune system. TO This group of complications includes, first of all, allergic reactions. The reasons for the development of hypersensitivity may be the drug itself, its decay products, as well as the complex of the drug with whey proteins. The occurrence of such complications depends on the properties of the drug itself, on the method and frequency of its administration, and on the patient's individual sensitivity to the drug. Allergic reactions develop in about 10% of cases and manifest as rash, itching, urticaria, Quincke's edema. Such a severe form of allergy manifestation as anaphylactic shock is relatively rare. This complication is more often given by beta-lactams.(penicillins), rifampicins. Sulfonamides can cause delayed-type hypersensitivity. The prevention of complications consists in a careful collection of an allergic anamnesis and the appointment of drugs in accordance with the individual sensitivity of the patient. In addition, antibiotics have some immunosuppressive effect and can contribute to the development of secondary immunodeficiency and the weakening of immunity.
Endotoxic shock (therapeutic). This is a phenomenon that occurs in the treatment of infections caused by Gram-negative bacteria. Administration of antibiotics causes cell death and destruction, and the release of large amounts of endotoxin. This is a natural phenomenon, which is accompanied by a temporary deterioration in the clinical condition of the patient.
Interaction with other drugs. Antibiotics can help potentiate the action or inactivate other drugs (for example, erythromycin stimulates the production of liver enzymes, which begin to rapidly metabolize drugs for various purposes).
Side effects on microorganisms.
The use of antimicrobial chemotherapy drugs has not only a direct inhibitory or detrimental effect on microbes, but can also lead to the formation of atypical forms of microbes (for example, the formation of L -forms of bacteria or changes in other properties of microbes, which greatly complicates the diagnosis of infectious diseases) and persistent forms of microbes. The widespread use of antimicrobial drugs also leads to the formation of antibiotic dependence (rarely) and drug resistance - antibiotic resistance (quite often).

Complications of antibiotic therapy

allergic reactions

Toxic effect of antibiotics

Adverse reactions due to the direct pharmacodynamic action of antibiotics

ALLERGIC REACTIONS

Allergy is understood as an altered reaction of the body to the action of foreign substances that occurs after

previous contact with them or due to the high hereditary sensitivity of the organism (Cooke, 1935).

Allergic reactions are not related to the pharmacological properties of drugs and occur only in people with increased

sensitivity (often sensitized).

In the body's immune response to any antigen, a sensitization phase (preparatory) and a manifestation phase are distinguished.

Allergy develops progressively: 1) the emergence of antibodies in response to antigenic stimulation; 2) complex formation

antigen-antibody in tissues, causing a rapid release of biologically active substances - histamine, heparin, serotonin;

3) the effect of these substances on blood vessels, bronchi, and the nervous system. Stages II and III are non-specific and the same when exposed to any

stimulus (antigen). This explains the stereotype of allergic reactions, the intensity and duration of which

depend on the localization of the reaction and the immune capabilities of the organism.

The antigenic properties of antibiotics are explained by the fact that they are the so-called. incomplete antigens - haptens (simple

chemical compounds). Haptens acquire antigenic properties only after binding to a protein in the body. It's being done

when bound to soluble proteins in the blood or cell membranes. It has been established that antibodies to penicillin belong to

classes IgG, IgM, IgE.

Clinical manifestations of allergic reactions can be realized immediately (these are the most dangerous reactions) or be

slow type. The main trigger of allergic reactions is damage to the tissues of the immunological

antigen-antibody reaction. At the same time, proteolytic and lipolytic enzymes are activated, histamine is released,

serotonin and other biologically active substances. They have a special effect on the apparatus of the nervous system, cause

increased vascular permeability, spasm of the smooth muscles of the bronchi, increase the hydrophilicity of the fibers of the loose connective tissue

tissues, leading to extensive edema. These pathogenetic mechanisms give allergic reactions a special,

sometimes very bright coloring and determine a complex set of clinical manifestations.

We have already emphasized that allergic reactions reflect the individual properties of the organism, and not pharmacological ones.

characteristics of the drug. However, more often these reactions occur with repeated administration of certain substances,

sensitizing the body, even with the introduction of negligible amounts (hundredths and thousandths of a gram). State

sensitization can persist for many months and years. Sensitization can also be caused by structurally similar

chemicals ("cross-sensitization"). An example is cross-sensitization with sulfonamides,

streptomycin and penicillin. This phenomenon explains cases of severe allergic reactions and even

anaphylactic shock with the first (single) administration of penicillin. It has now been found that the development

allergic reactions to medications, an individual predisposition, usually a family one, matters -

allergic constitution.

Types of allergic reactions.

Anaphylactic shock

Anaphylactic shock is the most formidable complication requiring rapid diagnosis and immediate treatment.

measures. It usually develops very quickly. It may be preceded by prodromal phenomena: itching, urticaria,

angioedema.

The main symptoms of anaphylactic shock are: drop in blood pressure up to collapse with tachycardia or

bradycardia, loss of consciousness, swelling of the face and mucous membranes, urticaria, rarely vomiting and diarrhea. For severe forms

observed intestinal bleeding, dyspnea, cerebral edema, liver damage, coma. Predisposition

organism to the development of shock is more pronounced in patients who previously suffered from various allergic diseases.

(bronchial asthma, hay fever, etc.).

Death from anaphylactic shock can occur in the first minutes and hours after the administration of an antibiotic. However,

cases where patients died a few days or weeks after the end of treatment.

Serum sickness syndrome.

Severe, sometimes irreversible or difficult to eliminate reactions of a generalized nature include the so-called

serum sickness, manifested by various skin reactions, angioedema, joint pain,

arthralgia, fever, blood eosinophilia, enlarged spleen and lymph nodes. The earliest

a symptom is swelling of the lymph nodes, sometimes in combination with an inflammatory-necrotic reaction at the site

introductions. (phenomenon of Artyus-Sakharov). In most cases, upon discontinuation of antibiotic therapy, serum

disease disappears without special treatment. In protracted cases, desensitizing therapy is indicated, the use of

antihistamines and hormonal drugs.

Skin lesions.

Skin and mucous membrane lesions of an allergic nature can be of a different nature.

Rash - macular, spotty roseola, maculopapular, macular spotted (like scarlet fever) - more often appears

with the introduction of penicillin to patients with hypersensitivity or previously sensitized. These reactions are easy

are removable and disappear after the abolition of the antibiotic and the appointment of deallergizing agents (diphenhydramine, pipolfen, chloride

calcium). However, in rare cases, reactions from the skin and mucous membranes are very persistent, and a long

treatment with the use of active and potent deallergizing agents. The most effective application

corticosteroid hormones - prednisone, prednisolone, triamcinolone, etc. - in doses dictated by the severity of the resulting

allergic reaction.

Dermatitis: erythematous, urticarial, or bullous rash (exfoliative dermatitis, sometimes generalized)

Contact dermatitis is most common in antibiotic workers and medical personnel with

constant contact with an antibiotic (especially penicillin, streptomycin, tetracycline, chloramphenicol, as well as other

antibiotics). Contact dermatitis can also occur when ointments or solutions containing antibiotics are applied to the skin,

their introduction intradermally or subcutaneously to determine sensitization to drugs.

Hives can be observed both after local and after systemic (parenteral, oral) administration of antibiotics

and is one of the most frequent allergic complications of antibiotic therapy (most often with penicillin therapy).

Urticaria occurs early (minutes, hours), and sometimes many days or weeks after antibiotic administration.

Angioedema (Quincke's edema) is localized (swelling of the lips, eyelids, face) or extends to a number of

areas (larynx, trachea, lungs). Angioedema may have independent significance or be a component

part of a general allergic reaction to the administration of antibiotics.

Photodermatoses - skin lesions caused by certain antibacterial drugs and manifested after

exposure to sunlight.

Determination of sensitivity to antibiotics.

The skin test is as follows. A drop of antibiotic solution is applied to the flexor surface of the forearm,

redness more than 1 cm in diameter, the reaction is rated as weakly positive (+) if the redness and papule are positive

(++) if multiple papules, vesicles, diffuse hyperemia - sharply positive (+++). In cases of sharply increased

sensitivity, a general reaction may occur - urticaria, urticaria rash all over the body, etc.

An intradermal test consists in the intradermal administration of an antibiotic solution (200-2000 units of penicillin) in 0.2 ml

physiological solution. An antibiotic is injected on the flexor surface of the forearm, on the other hand on a symmetrical

site injected with 0.2 ml of saline. The appearance of hyperemia (the size of the papule is more than 3 kopecks), swelling,

sometimes rashes at the injection site are regarded as a positive test.

Skin tests do not always give an immediate reaction: it may take 24-48 hours to show up.

TOXIC EFFECT OF ANTIBIOTICS.

Neurotoxic reactions

Neurotoxic phenomena occur after the use of antibiotics of a number of groups and manifest themselves:

1) damage to the auditory branches of the VIII pair of cranial nerves (monomycin, kanamycin, neomycin, streptomycin,

florimycin, ristomycin);

2) action on the vestibular apparatus (streptomycin, florimycin, kanamycin, neomycin, gentamicin). toxic

the action of streptomycin and other aminoglycosides on the VIII pair of cranial nerves is expressed in hearing loss and vestibular

disorders. In the nature of lesions of the organ of hearing, there is a difference between streptomycin and neomycin. During treatment

streptomycin, these reactions are mostly temporary (in some cases, persistent and

progressive lesion of the VIII pair of cranial nerves). Many TB patients are able to tolerate

complications of streptomycin injection within a few months. Neomycin causes complications much more often, in more

pronounced and persistent. They can occur after 7-10 days of using this drug. Considering this

fact, neomycin can only be applied topically and orally;

3) damage to the optic nerve (streptomycin, levomycetin, cycloserine, polymyxin);

4) the development of polyneuritis (streptomycin, polymyxin, amphotericin B, cycloserine);

5) the occurrence of paresthesia, headaches, dizziness, ataxia (polymyxin, streptomycin, cycloserine,

amphotericin B);

6) the development of various lesions of the central nervous system (cycloserine, polymyxin, griseofulvin, amphotericin B,

penicillin, streptomycin);

7) the occurrence of neuromuscular blockade (aminoglycosides, polymyxin);

8) direct toxic effect with intralumbar administration, manifested in the form of hallucinations,

epileptiform seizures, convulsions of individual muscle groups and general muscle hypertension (penicillin, streptomycin,

tetracycline, levomycetin and a number of other antibiotics). Neurotoxic reactions may occur with high doses.

benzylpenicillin (intravenously more than 40,000,000 IU per day).

Nephrotoxic reactions may accompany treatment with polymyxin, amphotericin B, neomycin, monomycin,

kanamycin, gentamicin, sisomycin, tobramycin, streptomycin, cephaloridine, griseofulvin, ristomycin,

sulfonamides.

Patients with impaired renal excretory function are particularly susceptible to the nephrotoxic effect of drugs, which

due to their cumulation and the creation of high concentrations in the blood due to impaired excretion. In case of violation

excretory function of the kidneys, the nephrotoxicity of many drugs increases with the simultaneous spread of toxic

action on the liver. In these cases, it is necessary to prescribe drugs with a less pronounced nephrotoxic effect and in the first place

turn penicillins and cephalosporins.

Penicillins - natural and their semi-synthetic derivatives - even in large doses are relatively low-toxic.

Cephalosporins. Nephrotoxic reactions are most often observed with the use of "old" cephalosporins:

cephalothin and cephaloridine (the latter with greater frequency). When using cephaloridine in high doses, severe

lesions of the renal tubules (up to necrosis). The incidence and severity of nephrotoxicity increases with

combinations of cephalosporins with aminoglycosides. For cephalosporins II and III generations (cefazodin, cefamandol, cefoxitin,

cefuroxime, etc.), these reactions are less common.

Aminoglycosides . Nephrotoxicity refers to one of the side effects of this group of antibiotics.

Among the aminoglycosides most commonly used parenterally, kanamycin and

gentamicin and other new aminoglycosides (tobramycin, sisomycin, amikacin). With long-term treatment with these drugs and in

doses exceeding the usual daily dose, lesions of the proximal tubules may be observed, which is clinically

expressed in a decrease in glomerular filtration, the appearance of albuminuria, microhematuria, enzymuria. Application of these

antibiotics in renal failure requires great caution. When prescribing aminoglycosides,

constantly monitor kidney function and choose the optimal daily dose of antibiotics according to the criterion of both effectiveness and

harmlessness.

Polymyxins have a nephrotoxic effect, however, with normal kidney function and compliance with

With care in choosing doses, these phenomena can be minimized.

Ristomycin, Viomycin (florimycin) are potentially nephrotoxic substances. These drugs should

use only in cases where other less toxic antibiotics do not give a therapeutic effect.

Tetracyclines do not have a direct nephrotoxic effect, however, in patients with renal failure

may increase the level of urea in the blood. In severe renal failure, tetracyclines can cause

azotemia, acidosis, vomiting. When using expired tetracycline preparations containing products

degradation of anhydrotetracycline and epianhydrotetracycline, Fanconi syndrome may develop (nausea, vomiting, albuminuria,

acidosis, glucosuria, aminoaciduria). At the same time, degenerative changes are observed in the distal parts of the renal tubules;

glomeruli remain intact. The phenomena are usually reversible.

Hepatotoxic events. Many antibiotics accumulate in high concentrations in bile (tetracyclines,

erythromycin, rifampicin) and can cause liver damage.

Hepatitis associated with direct toxic or toxic-allergic action of sulfonamides has been described. Since the liver

has a detoxifying function, and the kidneys have an excretory function, often both of these organs can be a simultaneous object

side effects of drugs. In case of any violations of the function of these systems, one must keep in mind the possibility of developing toxic

side effects. Accordingly, the physician should carefully monitor the development of these symptoms and choose less

toxic agent, reduce the dose or avoid prescribing drugs with possible side effects on the liver and kidneys. At

the use of amphotericin B can cause hepatitis, with the appointment of nitrofurans, lincomycin - the phenomenon of jaundice; at

treatment with some salts of erythromycin (estolate) - cholestatic hepatitis.

Severe liver damage in the form of fatty infiltration of liver cells can be observed when using large

doses of tetracyclines, especially those administered parenterally. Although these phenomena are usually reversible, in the presence of

the patient's history of organic liver damage or if hepatotoxic events are detected during the application

tetracycline antibiotic should be discontinued. To prevent the possibility of liver damage is not recommended

administer intravenously tetracycline at a daily dose of more than 1 g.

Described damage to the liver and pancreas in the treatment of tetracyclines in women suffering from pyelonephritis, in

period of pregnancy.

The hepatocellular form of drug jaundice is characteristic of griseofulvin, streptomycin, tetracyclines, amphotericin

B, florimycin and other drugs. Side effects stop after discontinuation of the drug.

Toxic effect on the gastrointestinal tract of a number of antibiotics (tetracycline, erythromycin, griseofulvin,

amphotericin B, fusidine, etc.), associated with their irritating effect on the mucous membranes, manifests itself in the form of nausea,

vomiting, anorexia, pain in the abdomen, diarrhea, etc. Usually these phenomena are not so pronounced as to cancel

antibiotics. However, with often joining dysbacteriosis under the influence of broad-spectrum antibiotics, as well as

lincomycin and clindamycin can cause serious complications up to pseudomembranous enterocolitis.

Influence on the hematopoietic system. Inhibition of hematopoiesis in the form of hypoplastic anemia is observed in rare cases.

cases with the use of levomycetin and amphotericin B, hemolytic anemia - with the use of levomycetin, streptomycin,

aplastic anemia - when using chloramphenicol. Leukopenia with agranulocytosis has been described during treatment with levomycetin,

ristomycin, griseofulvin, thrombocytopenia - when using ristomycin, levomycetin, rifampicin. Usually,

hematopoiesis is restored after the cessation of treatment. Severe bone marrow damage is observed during treatment

chloramphenicol, especially with its long-term use.

In the development of agranulocytosis and hypoplasia of hematopoiesis, the role of autoimmune mechanisms or a decrease in

resistance of blood cells to drugs due to enzyme deficiency (according to the type of development of some

hemolytic anemia, for example, drug-induced hemoglobinuria, etc.). Given the great rarity of hematopoietic hypoplasia in

bone marrow defect. Antibiotics in this case can play the role of a push in the implementation of the process.

With the greatest frequency, severe lesions of hematopoiesis (aplastic anemia) occur under the influence of chloramphenicol.

Anemia may be hypoplastic or aplastic with thrombocytopenia and agranulocytosis leading to

lethal outcomes. Based on the possibility of such severe phenomena, indications for the use of chloramphenicol should be strictly

limit and use the drug only under the supervision of a doctor, in a hospital, in cases where it is impossible to prescribe other, less

toxic substances.

Embryotoxic action of antibiotics - side effects of drugs on the fetus, associated with their penetration through

placental barrier. Cases of hearing damage in newborns are described in the treatment of pregnant women with streptomycin, hearing and kidney disease.

when treated with neomycin and kanamycin. Under the influence of tetracycline, when administered to pregnant women, pigmentation may occur.

teeth and damage to tooth enamel "increased susceptibility to caries in children. Described the effect on the growth of fetal bones (slowing

skeletal formation) when high doses of tetracyclines are administered to pregnant women. Due to the possibility of toxic effects on the fetus

for 3-6 weeks. before childbirth, the use of chloramphenicol, tetracycline, streptomycin, kanamycin and other drugs is contraindicated.

SIDE EFFECTS ASSOCIATED WITH THE BIOLOGICAL ACTION OF ANTIBIOTICS

This group includes superinfections caused by the biological action of antibiotics and nosocomial infections, and

also side effects associated with a violation of the composition of the so-called normal microflora of the patient's body

(dysbacteriosis), bacteriolysis reaction (Jarish-Herxheimer).

Superinfections can be both endogenous and exogenous. During antibiotic therapy, providing

cure of the main process, at the same time the normal microflora sensitive to the prescribed drugs is suppressed.

Many apathogenic or opportunistic microorganisms begin to multiply intensively, and can become a source of new

diseases (endogenous superinfection).

Endogenous superinfections can be caused by various microorganisms - staphylococci, Pseudomonas aeruginosa,

Proteus, Enterobacter, Serrations, Escherichia coli, anaerobes, pathogenic fungi, etc., naturally insensitive to

given antibiotic or acquired resistance during antibiotic therapy.

The form of the course of superinfections and their localization can be different: meningitis, brain abscesses (due to endocarditis

and sepsis), lesions of the urinary tract, gastrointestinal tract, biliary tract, respiratory tract, ENT organs, mucous membranes

shells and skin, eyes, etc.

Exogenous superinfection (as a result of secondary infection) may be due to the same type of microorganism,

which causes the underlying pathological process, but with a different degree of sensitivity to antibiotics, as well as a new species

pathogen. This phenomenon is observed in the treatment of diphtheria, pneumonia, tuberculosis, scarlet fever and can serve as a source of

Like any drugs, almost every group of antimicrobial chemotherapy drugs can have side effects, and on the macroorganism, and on microbes, and on other drugs.

Complications from the microorganism

The most common complications of antimicrobial chemotherapy are:

Toxic effect of drugs. As a rule, the development of this complication depends on the properties of the drug itself, its dose, route of administration, the patient's condition and manifests itself only with prolonged and systematic use of antimicrobial chemotherapeutic drugs, when conditions are created for their accumulation in the body. Especially often such complications occur when the target of the drug is processes or structures that are similar in composition or structure to similar structures of macroorganism cells. Children, pregnant women, as well as patients with impaired liver and kidney function are especially susceptible to the toxic effect of antimicrobial drugs.

Adverse toxic effects can manifest as neurotoxic (for example, glycopeptides and aminoglycosides have an ototoxic effect, up to complete hearing loss due to effects on the auditory nerve); nephrotoxic (polyenes, polypeptides, aminoglycosides, macrolides, glycopeptides, sulfonamides); general toxic (antifungal drugs - polyenes, imidazoles); oppression of hematopoiesis (tetracyclines, sulfonamides, levomycetin / chloramphenicol, which contains nitrobenzene - a suppressor of bone marrow function); teratogenic [aminoglycosides, tetracyclines disrupt the development of bones, cartilage in the fetus and children, the formation of tooth enamel (brown teeth), levomycetin / chloramphenicol is toxic to newborns in which liver enzymes are not fully formed ("grey baby syndrome"), quinolones - act on developing cartilage and connective tissue].

Warning complications consists in the rejection of drugs that are contraindicated for this patient, control over the state of the functions of the liver, kidneys, etc.

Dysbiosis (dysbacteriosis). Antimicrobial chemotherapy drugs, especially broad-spectrum ones, can affect not only infectious agents, but also sensitive microorganisms of the normal microflora. As a result, dysbiosis is formed, therefore, the functions of the gastrointestinal tract are disturbed, beriberi occurs, and a secondary infection may develop (including endogenous, for example, candidiasis, pseudomembranous colitis). Warning The consequences of such complications consist in prescribing, if possible, drugs with a narrow spectrum of action, combining the treatment of the underlying disease with antifungal therapy (for example, the appointment of nystatin), vitamin therapy, the use of eubiotics, etc.

Negative effect on the immune system. This group of complications includes, first of all, allergic reactions. The reasons for the development of hypersensitivity may be the drug itself, its decay products, as well as the complex of the drug with whey proteins. The occurrence of such complications depends on the properties of the drug itself, on the method and frequency of its administration, and on the patient's individual sensitivity to the drug. Allergic reactions develop in about 10% of cases and manifest as rash, itching, urticaria, Quincke's edema. Such a severe form of allergy manifestation as anaphylactic shock is relatively rare. This complication is more often given by beta-lactams (penicillins), rifampicins. Sulfonamides can cause delayed-type hypersensitivity. Warning Complications consists in a careful collection of an allergic anamnesis and the appointment of drugs in accordance with the individual sensitivity of the patient. In addition, antibiotics have some immunosuppressive effect and can contribute to the development of secondary immunodeficiency and weakening of the immune system.

Endotoxic shock (therapeutic). This is a phenomenon that occurs in the treatment of infections caused by Gram-negative bacteria. Administration of antibiotics causes cell death and destruction, and the release of large amounts of endotoxin. This is a natural phenomenon, which is accompanied by a temporary deterioration in the clinical condition of the patient.

Interaction with other drugs. Antibiotics can help potentiate the action or inactivate other drugs (for example, erythromycin stimulates the production of liver enzymes, which begin to rapidly metabolize drugs for various purposes).

Side effects on microorganisms.

The use of antimicrobial chemotherapy drugs has not only a direct inhibitory or detrimental effect on microbes, but can also lead to the formation of atypical forms of microbes (for example, the formation of L-forms of bacteria or a change in other properties of microbes, which greatly complicates the diagnosis of infectious diseases) and persistent forms of microbes. The widespread use of antimicrobial drugs also leads to the formation of antibiotic dependence (rarely) and drug resistance - antibiotic resistance (quite often). Principles of rational antibiotic therapy.

Prevention of the development of complications consists, first of all, in compliance with principles of rational antibiotic therapy(antimicrobial chemotherapy):

microbiological principles. Before prescribing the drug, it is necessary to establish the causative agent of the infection and determine its individual sensitivity to antimicrobial chemotherapeutic drugs. According to the results of the antibiogram, the patient is prescribed a narrow-spectrum drug that has the most pronounced activity against a specific pathogen, at a dose 2-3 times higher than the minimum inhibitory concentration. If the causative agent is still unknown, then drugs of a broader spectrum are usually prescribed, which are active against all possible microbes that most often cause this pathology. Correction of treatment is carried out taking into account the results of bacteriological examination and determination of the individual sensitivity of a particular pathogen (usually after 2-3 days). It is necessary to start treatment of the infection as early as possible (firstly, at the beginning of the disease there are fewer microbes in the body, and secondly, the drugs are more active on growing and multiplying microbes).

pharmacological principle. The characteristics of the drug are taken into account - its pharmacokinetics and pharmacodynamics, distribution in the body, frequency of administration, the possibility of combining drugs, etc. Doses of drugs should be sufficient to ensure microbostatic or microbicidal concentrations in biological fluids and tissues. It is necessary to present the optimal duration of treatment, since clinical improvement is not a basis for discontinuation of the drug, because pathogens may persist in the body and there may be a relapse of the disease. The optimal routes of drug administration are also taken into account, since many antibiotics are poorly absorbed from the gastrointestinal tract or do not penetrate the blood-brain barrier.

clinical principle. When prescribing a drug, it is taken into account how safe it will be for a given patient, which depends on the individual characteristics of the patient's condition (severity of infection, immune status, gender, pregnancy, age, state of liver and kidney function, concomitant diseases, etc.) , life-threatening infections, timely antibiotic therapy is of particular importance. Such patients are prescribed combinations of two or three drugs to ensure the widest possible spectrum of action. When prescribing a combination of several drugs, one should know how effective the combination of these drugs will be against the pathogen and how safe for the patient, i.e., so that there is no antagonism of drugs in relation to antibacterial activity and there is no summation of their toxic effects.

epidemiological principle. The choice of a drug, especially for an inpatient, should take into account the state of resistance of microbial strains circulating in a given department, hospital, and even the region. It should be remembered that antibiotic resistance can not only be acquired, but also lost, while the natural sensitivity of the microorganism to the drug is restored. Only natural stability does not change.

pharmaceutical principles. It is necessary to take into account the expiration date and follow the rules for storing the drug, since if these rules are violated, the antibiotic can not only lose its activity, but also become toxic due to degradation. The cost of the drug is also important.

41.Allergic tests, their essence, application.

Allergic tests- biological reactions for the diagnosis of a number of diseases, based on the increased sensitivity of the body caused by the allergen.

For many infectious diseases due to the activation of cellular immunity, an increased sensitivity of the body to pathogens and their metabolic products develops. Allergic tests used to diagnose bacterial, viral, protozoal infections, fungal infections and helminthiases are based on this. Allergic tests are specific, but often they are positive in those who have been ill and vaccinated.

All allergic tests are divided into two groups- samples in vivo and in vitro.

To the first groupin vivo ) include skin tests performed directly on the patient and detecting an allergy of immediate (after 20 minutes) and delayed (after 24-48 hours) types.

Allergic testsin vitro based on the detection of sensitization outside the patient's body. They are used when, for one reason or another, skin tests cannot be performed, or in cases where skin reactions give unclear results.

For allergy testing allergens are used - diagnostic preparations designed to detect specific sensitization of the body. Infectious allergens used in the diagnosis of infectious diseases are purified filtrates of broth cultures, less often suspensions of killed microorganisms or AG isolated from them.

Skin tests.infectious allergens administered, as a rule, intradermally or cutaneously, by rubbing into scarified areas of the skin. With the intradermal method, 0.1 ml of the allergen is injected into the middle third of the anterior surface of the forearm with a special thin needle. After 28 - 48 hours, the results of the HRT reaction are evaluated, determining the size of the papule at the injection site.

Non-infectious allergens(plant pollen, household dust, food products, drugs and chemicals) are injected into the skin by injection (prick test), skin by scarification and rubbing, or intradermal injection of a diluted allergen solution. ICN is used as a negative control, and histamine solution is used as a positive control. The results are taken into account within 20 minutes (GNT) according to the size of the papule (sometimes up to 20 mm in diameter), the presence of edema and itching. Intradermal tests are performed in case of a negative or doubtful result of the prick test. Compared with the latter, the dose of the allergen is reduced by 100-5000 times.

Skin tests for the presence of HRT are widely used to detect infection of people with Mycobacterium tuberculosis (Mantoux test), pathogens of brucellosis (Burne test), leprosy (Mitsuda reaction), tularemia, glanders, actinomycosis, dermatomycosis, toxoplasmosis, some helminthiases, etc.

samplesin vitro . These research methods are safe for the patient, sensitive enough, allow to quantify the level of allergization of the body.

Currently, tests have been developed to determine sensitization based on reactions T- and B-lymphocytes, tissue basophils, identification of common specific IgE in blood serum, etc. These include reactions of inhibition of migration of leukocytes and blast transformation of lymphocytes, specific rosette formation, Shelley's basophil test, degranulation reaction of tissue basophils, as well as allergosorbent methods (determination of specific IgE in serum).

Leukocyte migration inhibition test (RTML). RTML is based on the suppression of the migration of monocytes and other leukocytes under the action of mediators produced by sensitized lymphocytes in the presence of a specific allergen.

Lymphocyte blast transformation reaction (RBT). This reaction is based on the ability of normal peripheral blood lymphocytes to enter mitosis and turn into blast forms when they are cultivated. in vitro Under the influence specific factors - allergens and non-specific Mitogenesis stimulators - mitogens (phytohemagglutinin, concanavalin A, lipopolysaccharides and other substances).

Reaction of specific rosette formation. Rosettes are characteristic formations that arise in vitro as a result of adhesion of erythrocytes to the surface of immunocompetent cells. Rosette formation can occur spontaneously, since human T-lymphocytes contain receptors for ram erythrocytes. Spontaneous rosette formation in healthy people is 52 - 53% and serves as an indicator of the functional state of T-lymphocytes. This phenomenon is also reproduced if erythrocytes are used, on which the corresponding allergens are fixed.

Degranulation reaction of tissue basophils. The technique is based on the fact that under the action of the allergen, degranulation of rat tissue basophils, previously sensitized by cytophilic antibodies from the patient's blood serum, occurs.

Shelley's basophil test. It is known that human or rabbit basophilic granulocytes are also degranulated in the presence of the patient's serum and an allergen to which the patient is sensitive.

Definition of antibody classIgE in vitro. Laboratory diagnosis of diseases based on HIT is based on the determination of allergen-specific IgEanti-IgE. When using a radioactive label, the method is called the radioallergosorbent test (PACT), but more often an enzyme or fluorescent substance (FAST) is used as a label. Analysis time - 6 - 7 hours. The principle of the method: a known allergen fixed on a solid base is incubated with the patient's blood serum; serum specific IgEanti-IgE bind to the allergen and thus remain fixed on the base and can interact specifically with added labeled anti-IgE.